F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells

Mookerjee‐Basu, Jayati; Vantourout, Pierre; Martinez, Laurent O.; Fougère, Bertrand; Collet, Xavier; Philouze, Christian; Peyrottes, Suzanne; Champagne, Éric

doi:10.4049/jimmunol.0904024

Cited by 52 publications

(39 citation statements)

References 36 publications

(45 reference statements)

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“…F1.ATPase-coated beads stably bound to an adenylated derivative of IPP, and promoted TCR aggregation, cytokine secretion, and cytotoxic activity (10). These studies collectively support the concept that activation of Vg9Vd2 T cells requires a certain density of membrane-bound phosphoantigens to induce efficient TCR signaling, which is necessary for the activation of their antitumor cytotoxic properties (4, 5, 7).…”

Section: T-cell Receptor Agonists For Activation Of Vg9vd2 T Cellssupporting

confidence: 58%

“…Although putative interactions between phosphoantigens and the Vg9Vd2 TCR have yet to be characterized, MookerjeeBasu and colleagues suggested that cell surface-bound F1.ATPase can act as a phosphoantigen-presenting molecule (10). F1.ATPase-coated beads stably bound to an adenylated derivative of IPP, and promoted TCR aggregation, cytokine secretion, and cytotoxic activity (10).…”

Section: T-cell Receptor Agonists For Activation Of Vg9vd2 T Cellsmentioning

confidence: 99%

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Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application

2010

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Abundant interferon-g secretion, potent cytotoxicity, and major histocompatibility complex-independent targeting of a large spectrum of tumors make gd T cells attractive mediators of cancer immunotherapy. However, a better understanding of the molecular mechanisms involved in tumor cell recognition and gd T-cell activation is required to improve the limited success of gd T-cell-mediated treatments. Here, we review key advances in basic knowledge made over the past 3 years, and summarize the results of gd T-cell-based clinical trials concluded to date. We also highlight new research directions on the basis of the modulation of receptors that control the function of gd T cells.

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Section: T-cell Receptor Agonists For Activation Of Vg9vd2 T Cellssupporting

confidence: 58%

Section: T-cell Receptor Agonists For Activation Of Vg9vd2 T Cellsmentioning

confidence: 99%

Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application

2010

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“…Alternatively, CD277 might promote recruitment of other receptors recognized by the V␥9V␦2 TCR, such as ecto-F1-ATPase, which is a known ligand for V␥9V␦2 TCR. 44,45 The restricted but mandatory implication of CD277 in the activation of particular human ␥␦ T-cell subsets brings to mind the mandatory role played by Skint-1, another member of the extended B7 receptor family, in the selection of murine intraepidermal ␥␦ T cells. [16][17][18] Although Skint-1 deficiency prevents differentiation of T cells expressing invariant V␥5V␦1 TCR, it has no effect on other ␥␦ or ␣␤ T-cell compartments.…”

Section: Discussionmentioning

confidence: 99%

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

Harly

Guillaume

Nédellec

et al. 2012

Blood

457

632

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Introduction␥␦ T cells are key players in the immune surveillance of cellular distress, thanks to their ability to recognize conserved determinants up-regulated after inflammation, infection, or cell transformation. 1,2 Although ␥␦ T-cell receptors (TCRs) contribute to detection of danger-associated determinants, ligands for these receptors have been identified in a few cases only. 3 Thus, the antigenic specificity of ␥␦ T cells and their fine activation modalities in response to cell stress remain largely unknown.One of the best studied ␥␦ T-cell subsets in humans expresses V␥9V␦2 TCR and predominates in blood, composing several percent of the whole peripheral lymphoid pool in most adults. V␥9V␦2 T cells are activated by nonpeptidic phosphorylated isoprenoid pathway metabolites, 4-6 hereafter referred to as phosphoagonists (PAg). Natural V␥9V␦2-stimulating PAg include isopentenyl pyrophosphate (IPP), 7 a metabolite of the mevalonate pathway found in mammalian cells and the desoxyxylulose phosphate pathway shared by many microorganisms, and hydroxy-methyl-butyl-pyrophosphate, 8 an intermediate of the latter pathway. PAg detection by ␥␦ T cells underlies their broad reactivity toward infected and transformed cells. Indeed, tumor cell recognition by V␥9V␦2 T cells is linked to enhanced production of the weak agonist IPP, resulting from increased cell metabolism and cholesterol biosynthesis. Accordingly, pharmacologic inhibitors of the mevalonate pathway that up-regulate (eg, aminobisphosphonates, NBP) or down-regulate (eg, statins) IPP production, respectively, increase or decrease antitumor V␥9V␦2 T-cell responses. 9,10 Moreover, because of the high V␥9V␦2 T cell-stimulating activity of the microbial agonist hydroxy-methyl-butyl-pyrophosphate, V␥9V␦2 T-cell responses are elicited by infected cells producing even traces of this PAg. 8 Although PAg-induced activation is restricted to V␥9V␦2 T cells and can be conferred by V␥9V␦2 TCR gene transfer, 11,12 attempts to detect cognate interactions between PAg and V␥9V␦2 TCR have failed so far. 13 So how V␥9V␦2 T cells sense PAg remains an enigma. PAg rapidly induce Ca 2ϩ signaling and activation of V␥9V␦2 T-cell clones, but this requires cell-to-cell contact, suggesting the implication of additional target cell surface receptors in this phenomenon. 11,14 PAg elicit V␥9V␦2 T-cell responses against basically all human cells, irrespective of their tissue origin, but do not induce recognition of any murine target cells. Therefore, the putative target cell receptors involved in PAg-mediated T-cell activation are expected to be broadly expressed by human, but not murine, cells.Activation of antigen-stimulated T cells is tuned by interactions involving T cell-derived CD28-related receptors and target cellderived B7-related counter-receptors, 15 which family includes members, such as Skint and butyrophilin (BTN) receptors. The mandatory role played by Skint-1 in the intrathymic positive There is an Inside Blood commentary on this article in this issue.The online version of this...

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“…In an attempt to reconcile the established reactivity of Vc9Vd2 T cells to non-peptidic pAgs and these new observations of alternative stress-induced ligands, experiments were carried out to demonstrate that ATP synthase can also potentially bind to pAgs, and it was concluded that it seemingly has the appropriate features to function as a possible pAg presenting molecule for Vc9Vd2 T cells. 76 More recently, another putative Vc9Vd2 T cell tumor antigen, human MutS homologue 2 (MSH2), was identified using a peptide-based affinity screening system for the CDR3 of the d chain. 77 MSH2 is normally located in the nucleus where it functions as a DNA mismatch repair gene, but it is often mutated in a number of different types of epithelial cancers and can be ectopically expressed.…”

Section: Vd2 T Cells: To Know the Complex Burden Of Being Humanmentioning

confidence: 99%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

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F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells

Abstract: Material

Cited by 52 publications

References 36 publications

Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application

Targeting γδ T Lymphocytes for Cancer Immunotherapy: From Novel Mechanistic Insight to Clinical Application

Key implication of CD277/butyrophilin-3 (BTN3A) in cellular stress sensing by a major human γδ T-cell subset

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

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